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Seroprevalence of Lyme Borreliosis in Europe:
Results from a Systematic Literature Review (2005–2020)
Leah Burn,
1
Andreas Pilz,
2
Andrew Vyse,
3
Aura Victoria Gutie´ rrez Raba´,
4
Frederick J. Angulo,
5
Thao Mai Phuong Tran,
4
Mark A. Fletcher,
6
Bradford D. Gessner,
5
Jennifer C. Moı¨si,
7
and James H. Stark
5
Abstract
Background: Lyme borreliosis (LB), a tick bite-transmitted infection caused by Borrelia burgdorferi sensu lato
(Bbsl) complex spirochetes, is the most common tickborne disease in Europe. Studies in European countries
have reported LB seroprevalence (prevalence of antibodies to Bbsl infection) and diagnostic strategies used for
testing. We conducted a systematic literature review to summarize contemporary LB seroprevalence in Europe.
Methods: PubMed, Embase, and CABI Direct (Global Health) databases were searched from 2005 to 2020 to
identify studies reporting LB seroprevalence in European countries. Reported single-tier and two-tier test results
were summarized; algorithms (standard or modified) were used to interpret final test results from studies that
used two-tier testing.
Results: The search yielded 61 articles from 22 European countries. Studies used a range of diagnostic testing
methods and strategies (48% single-tier, 46% standard two-tier, and 6% modified two-tier). In 39 population-
based studies, of which 14 were nationally representative, seroprevalence estimates ranged from 2.7% (Norway)
to 20% (Finland). There was substantial heterogeneity among studies in terms of design, cohort types, periods
sampled, sample sizes, and diagnostics, which limited cross-study comparisons. Nevertheless, among studies
that reported seroprevalence in persons with greater exposure to ticks, LB seroprevalence was higher among
these groups than in the general population (40.6% vs. 3.9%). Furthermore, among studies that used two-tier
testing, general population LB seroprevalence was higher in Western Europe (13.6%) and Eastern Europe (11.1%)
than in Northern Europe (4.2%) and Southern Europe (3.9%).
Conclusion: Despite variations in LB seroprevalence between and within European subregions and countries,
high seroprevalence was observed in certain geographic regions and particular risk groups, suggesting signifi-
cant disease burden and supporting the need for improved, targeted public health interventions such as vac-
cination. Harmonized approaches to serologic testing and more nationally representative seroprevalence studies
are needed to better understand the prevalence of Bbsl infection in Europe.
Keywords: Lyme borreliosis, seroprevalence, seropositivity, Europe, epidemiology, diagnostics
1
P95 Pharmacovigilance & Epidemiology, Princeton, New Jersey, USA.
2
Pfizer Global Medical Affairs, Vaccines, Vienna, Austria.
3
Pfizer Vaccines Medical, Walton Oaks, United Kingdom.
4
P95 Pharmacovigilance & Epidemiology, Leuven, Belgium.
5
Pfizer Vaccines Medical Development, Scientific and Clinical Affairs, Collegeville, Pennsylvania, USA.
6
Pfizer Emerging Markets Medical Affairs, Vaccines, Paris, France.
7
Pfizer Medical Development, Scientific and Clinical Affairs, Vaccines, Paris, France.
Leah Burn et al. 2023; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative
Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
VECTOR-BORNE AND ZOONOTIC DISEASES
Volume 23, Number 4, 2023
Mary Ann Liebert, Inc.
DOI: 10.1089/vbz.2022.0069
195
Introduction
Lyme borreliosis (LB), the most common tickborne
disease in Europe, is caused by an infection with spiro-
chetes of the Borrelia burgdorferi sensu lato (Bbsl) complex,
which is transmitted to humans through the bite of a vector-
competent, infected tick (Bennet et al. 2007, Bobe et al.
2021). Although a proportion of infections are reported to be
asymptomatic (median proportion of asymptomatic infected
persons from studies in Europe was 50%) (Stanek et al. 2011,
Hofhuis et al. 2013, Markowicz et al. 2021), asymptomatic
persons can still seroconvert (Huegli et al. 2011, Hofhuis
et al. 2013, Wilhelmsson et al. 2016). Clinical manifestations
of LB typically begin with development of erythema migrans
at the site of a tick bite, with signs and symptoms such as
fatigue, fever, arthralgia, and myalgia (Bobe et al. 2021). The
infection may then disseminate and present with a range of
clinical syndromes, including neurologic (Lyme neuroborre-
liosis), rheumatologic (Lyme arthritis), dermatologic (acro-
dermatitis chronica atrophicans), hematologic (borrelial
lymphocytoma), and/or cardiac (Lyme carditis) (Steere et al.
2016).
The distribution and density of vector-competent ticks
infected with clinically relevant Bbsl in Europe has been
widely investigated. Vector-competent ticks mainly include
Ixodes ricinus and Ixodes persulcatus (Margos et al. 2019,
Perry 2021), and eight clinically relevant genospecies
belonging to Bbsl complex have been reported: B. burgdor-
feri sensu stricto,Borrelia afzelii,Borrelia garinii,Borrelia
valaisiana,Borrelia lusitaniae,Borrelia bissettii,Borrelia
bavariensis,andBorrelia spielmanii (Rauter and Hartung
2005, Richter and Matuschka 2006, Margos et al. 2009). Living
or working in highly endemic geographic areas and under-
taking outdoor occupations or leisure activities (e.g., forestry
work, farming, hunting, hiking) lead to greater risk of exposure
(Piacentino and Schwartz 2002, Magnavita et al. 2022).
The serologic response to Bbsl infection begins with
immunoglobulin M (IgM) antibodies, which initially become
detectable within a few days to a few weeks after infection
(Steere et al. 2016). Immunoglobulin class switching occurs,
and immunoglobulin G (IgG) antibodies become detectable
within 1–2 months; serum IgG and IgM antibodies can still
be detected 10–20 years after infection (Kalish et al. 2001,
Peltomaa et al. 2003, Glatz et al. 2006). Most individuals
infected by Bbsl develop detectable antibodies; therefore,
serology is the standard laboratory method for confirming an
LB diagnosis (Wilske et al. 2007, Steere et al. 2016). Sero-
logic confirmation of an LB diagnosis uses a two-tier strategy
to optimize sensitivity and specificity (Fig. 1) (Branda and
Steere 2021). For standard two-tier testing, the first-tier
screen for IgG or IgM is an enzyme immunoassay (EIA; or
enzyme-linked immunoassay [ELISA]) or an immuno-
fluorescence assay (IFA).
To maximize specificity in the second tier, first-tier posi-
tive samples are then tested by western blot (WB) for IgM
and/or IgG (Branda and Steere 2021). EIAs that detect anti-
bodies to the highly conserved variable major protein-like
sequence expressed (VlsE) peptides can improve specificity
(Branda et al. 2013). Alternatively, modified two-tier testing
methods that use two or more different EIA or ELISA
methods as the second tier can improve diagnostic sensitivity
without sacrificing specificity (Branda and Steere 2021).
Population-level seroprevalence can be used to monitor
the prevalence of current or past infection in European
countries without public health surveillance for LB. Fur-
thermore, seroprevalence estimates, which indicate exposure
to Bbsl at some point, can be compared with the number of
surveillance-reported symptomatic LB cases to assess under-
ascertainment of human contact with vector-competent, Bbsl-
infected ticks. Seroprevalence data are capable of identifying
geographic localities and outdoor occupations or leisure
activities at higher risk of infection and monitoring population-
level changes over time, such as those related to public health
interventions. Consequently, we conducted a systematic lit-
erature review to obtain contemporary estimates of the sero-
prevalence of LB in Europe.
Methods
The methodology, search strategy, and inclusion and ex-
clusion criteria for the systematic literature review and analysis
are described in detail in a protocol developed by the Pfizer/P95
Lyme Review Group according to Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA, 2020)
guidelines and registered in PROSPERO (CRD42021236906).
Search strategy
We conducted a multidatabase, systematic literature review
across PubMed, Embase, and CABI Direct (Global Health)
databases from January 1, 2005, to November 20, 2020, using
the following search terms (with no language restrictions):
Lyme, Borrelia, and borreliosis. After duplicates were remo-
ved, titles and abstracts were screened independently by two
reviewers for their relevance to the study objectives, and the
selected full-text articles were assessed based on predefined
inclusion and exclusion criteria by two reviewers. Full-text
articles published in other European languages were trans-
lated into English using DeepL (DeepL SE 2021).
Inclusion and exclusion criteria
Articles reporting results of serologic testing for Bbsl
complex infection were included if the articles clearly rep-
orted a defined numerator (number of seropositive cases),
denominator (size of the population tested), and diagnostic
testing strategy based on at least one diagnostic test of either
an EIA or ELISA, IFA, or western immunoblot.
Health-economic and cost studies, studies of biomedical
mechanisms, mathematical models, and diagnostic guide-
lines, and studies without human serologic results were
excluded, as were data only in abstract form from confer-
ences, letters, perspective or opinion articles, or commen-
taries. Literature review articles were not included but were
scanned for additional references.
Articles retrieved using the above criteria were further
assessed to select articles reporting seroprevalence estimates.
Studies were included if they reported estimates of seropre-
valence (and not disease incidence) based on rigorous pop-
ulation sampling methods such as random, cross-sectional, or
survey cluster sampling. If multiple seroprevalence results
were obtained over time, only the first seroprevalence esti-
mate was used to avoid mixing seroprevalence with sero-
conversion or incidence. Studies were excluded if they
comprised participants who were selected for participation
196 BURN ET AL.
because they had suspected or confirmed LB or if they rep-
orted data from cohorts recruited based on tick bite exposure.
Data extraction
Relevant variables from selected articles were extracted
into DistillerSR (Evidence Partners 2021). A reviewer inde-
pendently confirmed the extraction by reviewing 20% of the
articles. Predefined outcomes of interest for extraction were
testing method, diagnostic strategy, results of serologic test-
ing, population characteristics, and risk status. All discre-
pancies were discussed and resolved by the authors. The
outcome of interest was seropositivity by at least one sero-
logic test. Population risk level was defined by likelihood of
exposure to ticks due to residence in specific regions or by
occupational or leisure activities.
Data interpretation and analysis
Study results were synthesized by relevant descriptive
variables and seroprevalence results. When studies used sev-
eral types of single-tier tests (e.g., measurement of IgM or
IgG), IgG tests results were preferred. This is because IgM-
based tests, although useful for clinical diagnosis of early
infection, are more likely to yield false positives (Branda and
Steere 2021). In this review, therefore, IgG results were used
to report seroprevalence. When studies used a two-tier test-
ing strategy, final test results were based on calculations from
standard or modified algorithms (Fig. 1). More prominence
was given to test results from two-tier strategies due to the
optimal sensitivity and specificity of this system (Branda and
Steere 2021).
The 95% confidence intervals (CIs) (Cisak et al. 2008) for
seroprevalence estimates were calculated using the binomial
exact CI for a single proportion. Seroprevalence results were
stratified by age, sex, and intracountry region (Supplemen-
tary Table S1).
We calculated the population-weighted mean seropre-
valence for each of the European regions using data available
for countries belonging to that region. If a study reported data
on both the national and regional levels, we used only the data
FIG. 1. Algorithm for the serologic testing of LB (Centers for Disease Control and Prevention 2011, Marques 2018, Branda
and Steere 2021). Overall test results should be used from two-tier testing, with the original denominator.
a
EIA or IFA WCS.
C6, C6 protein of the variable major protein-like sequence lipoprotein; EIA, enzyme immunoassay; IFA, immunofluores-
cence assay; IgG, immunoglobulin G; IgM, immunoglobulin M; LB, Lyme borreliosis; WCS, whole-cell sonicate.
SEROPREVALENCE OF LYME BORRELIOSIS IN EUROPE 197
on the national level as a summary of that country. For studies
that reported regional, subnational data only, seroprevalence
from the largest reported region was used to calculate the
weighted mean seroprevalence. We stratified weighted mean
seroprevalence by diagnostic strategy and antibody testing
method (Tables 5–8). Results were also stratified by exposure
risk group. A population was considered a high-risk group for
LB if it included a group with high exposure to ticks, such as
forestry workers, farmers, or residents in high-risk regions
(Tables 1–4).
As a secondary analysis, to explore the impact of risk
status on seroprevalence, seroprevalence odds ratios (ORs)
and corresponding 95% CIs were calculated in R using the
approximate Bayesian CIs (Laud 2021). The OR was calcu-
lated as seroprevalence of positive serologic test results in
the risk group under study (high risk of exposure to ticks)
compared with the seroprevalence in a control group (low
or unknown risk of exposure to ticks) (Supplementary
Table S2). Criteria used to classify study participants by their
risk of exposure to ticks is defined in Supplementary
Table S5. ORs >1 (with CIs also >1) indicate significantly
higher seroprevalence among the high-risk group compared
with the low-risk group.
Results
Search results
We included 61 articles from 22 European countries for
analysis (Fig. 2); of these countries, seven had only 1 study,
while Poland had 10 articles and Turkey had 11. The number
of publications by country is shown in a heat map (Fig. 3).
Fifty-two studies used a cross-sectional design, eight used a
prospective cohort design, and one used a retrospective co-
hort design. Some studies contained both groups, general and
high-risk populations (Supplementary Table S3).
A summary of the included articles with reported sero-
prevalence estimates and corresponding diagnostic tests and
strategies is provided (Tables 1–4). The results are organized
by European Region per World Health Organization (WHO)
Regional Classifications (Supplementary Table S4) (World
Health Organization 2022).
Study populations
Of the 61 total studies, 39 (64%) were population based,
with blood samples collected from the general population
(Supplementary Table S3), including office workers, healthy
FIG. 2. PRISMA flow diagram.
PRISMA, Preferred Reporting
Items for Systematic Reviews and
Meta-Analyses.
198 BURN ET AL.
volunteers, and patients without clinical suspicion of LB,
while 34 (56%) studies collected blood samples from popu-
lations with high risk of exposure to ticks (Supplementary
Tables S3 and S5), including hunters, forestry and field work-
ers, rangers, veterinarians, farmers and retired farmers, and
soldiers. Among the 39 population-based studies, 14 collec-
ted nationally representative blood samples from the general
population. Some studies were conducted among both gen-
eral and high-risk groups, so there was overlap (N>61).
Diagnostic testing strategies
Diagnostic testing methods and strategies varied among
studies (Tables 1–4). Many studies used more than one test.
Of the 61 studies, 28 used single-tier testing (23 used ELISA
or EIA; 5 used IFA), and 30 studies utilized standard two-tier
testing (ELISA with WB [IgG, IgM, or both]). Eight articles
reported seroprevalence as a combined result using IgM
and/or IgG detected by WB, and three studies used modified
two-tier testing, including two studies from Finland (whole-
cell sonicate IgG+C6 [C6 protein of the variable major
protein-like sequence lipoprotein] Lyme ELISA+IFA IgG)
and one study from Turkey (ELISA+enzyme-linked IFA
[IgG]).
Five of the 61 studies used the VlsE-based EIA as either
single-tier testing or part of a two-tier method. This included
two studies in Norway (Hjetland et al. 2014, Vestrheim et al.
2016), one in Slovakia (Bazovska
´et al. 2010), one in Turkey
(Gazi et al. 2016), and one in Poland (Pan
´czuk et al. 2019).
Many studies tested blood samples collected from partic-
ipants in more than one period. Tests included both com-
mercial (49 studies) and in-house (3 studies) assays; 8 studies
did not give information on the source.
Seroprevalence estimates by European region
Eastern Europe (Czech Republic, Hungary, Poland,
Russia, Slovakia, Slovenia, Ukraine)
Seroprevalence among general populations. Twenty-
three articles reported seroprevalence of LB in seven Eastern
European countries (Table 1) (Bazovska et al. 2005, Rojko
et al. 2005, Hajek et al. 2006, Biletska et al. 2008, Cisak et al.
2008, Buczek et al. 2009, Bazovska
´et al. 2010, Podsiadly
et al. 2011, Lakos et al. 2012, Machcin
´ska et al. 2013,
Kocbach and Kocbach 2014, Tokarska-Rodak et al. 2014,
Za
´kutna
´et al. 2015a, 2015b, Kuchynka et al. 2016, Magnaval
et al. 2016, Zaja˛c et al. 2017, Bura et al. 2018, Bus
ˇova
´et al.
2018, Kiewra et al. 2018, Kr
ˇı
´z
ˇet al. 2018, Pan
´czuk et al.
2019, Pawelczyk et al. 2019). National seroprevalence esti-
mates using a single-tier testing strategy on healthy persons
and/or indoor workers were 5% in Poland (ELISA IgG,
healthy blood donors) (Pawelczyk et al. 2019), 9.7% in
Slovenia (ELISA IgG) (Rojko et al. 2005), 10.3% in Russia
(ELISA IgG) (Magnaval et al. 2016), and 34.3% in Ukraine
(IFA IgG+IgM) (Biletska et al. 2008).
Seroprevalence in high-risk groups. The seroprevalence
of LB in populations with high-risk occupations using
FIG. 3. Heat map of number of publications by country from literature published between 2005 and 2020. N=61.
SEROPREVALENCE OF LYME BORRELIOSIS IN EUROPE 199
Table 1. Estimates of Lyme Borreliosis Seroprevalence in Eastern Europe from Published Literature, 2005–2020
Country
National or region
within country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Czech
Republic
Plzen, Vysocina,
South Bohemia,
Central
Bohemia, South
Moravia,
Moravia-Silesia
Kr
ˇı
´z
ˇet al.
(2018)
Cross-sectional
(1978–1989)
Cross-sectional
(2001)
Random 434 Serum bank
samples
b
Not described Single tier ELISA IgG 25.1
270 Serum bank
samples
b
Single tier ELISA IgG 10.3
Czech
Republic
Prague Hajek et al.
(2006)
Cross-sectional
(1995–1999)
Consecutive 890 Patients with
psychiatric
disorders
b
Mean (SD):
33.6 (13.9)
Single tier ELISA IgM
and/or IgG
35.7
Czech
Republic
Prague Kuchynka
et al. (2016)
Cross-sectional
(2013–2014)
Convenience 50 Adults with
normal left
ventricular
systolic function
and no history
suggestive of
myocarditis
b
Mean (SD):
67 (9)
Standard
two-tier
ELISA IgG
and/or
IgM+WB
14
Hungary National
c
Lakos et al.
(2012)
Cross-sectional
(1992–1995)
Convenience 1670 Forestry workers
d
Mean (SD):
40.7 (10.2)
Single tier ELISA
IgG+IgM
37.2
Poland Southern Podlasie
Lowland, Lublin
Polesie
Tokarska-
Rodak et al.
(2014)
Cross-sectional
(2013)
Not described 172 Forestry workers
d
Range: 25–72 Standard
two-tier
ELISA+WB
IgG and/or
IgM
54.9
104 Farmers
d
Standard
two-tier
ELISA+WB
IgG and/or
IgM
28.0
45 Persons not
occupationally
exposed to
ticks
b
Standard
two-tier
ELISA+WB
IgG and/or
IgM
5.0
Poland Warsaw Machcin
´ska
et al. (2013)
Cross-sectional
(2013)
Not described 90 Blood donors
b
Range: 18–70 Single tier ELISA IgM 2.2
ELISA IgG 10.0
Poland Six forest districts
in Ostro
´da
Kocbach and
Kocbach
(2014)
Cross-sectional
(2011–2012)
Convenience 332 Forestry workers
d
Mean (range):
37 (25–67)
Standard
two-tier
ELISA+WB
IgG
27.4
St. Jablonki 42 Standard
two-tier
ELISA+WB
IgG
11.9
Kudypy 47 Standard
two-tier
ELISA+WB
IgG
25.5
Wipsowo 79 Standard
two-tier
ELISA+WB
IgG
22.8
Wichrowo 54 Standard
two-tier
ELISA+WB
IgG
31.5
Iława 47 Standard
two-tier
ELISA+WB
IgG
21.3
Miłomłyn 63 Standard
two-tier
ELISA+WB
IgG
23.8
(continued)
200
Table 1. (Continued)
Country
National or region
within country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Poland Western Poland
(Mie˛ dzycho
´d)
Bura et al.
(2018)
Cross-sectional
(2014)
Not described 48 Forest rangers
d
Mean (SD):
45.0 (9.6)
Standard
two-tier
ELISA+WB
IgM
8.3
Standard
two-tier
ELISA+WB
IgG
37.5
Poland National
c
Pawelczyk
et al. (2019)
Cross-sectional
(2013/2016)
Not described 227 HIV-infected
persons
b
Mean (range):
33 (20–51)
Single tier ELISA IgM 29.1
ELISA IgG 4.8
199 Healthy blood
donors
b
Mean (range):
36 (18–71)
Single tier ELISA IgM 13.1
ELISA IgG 5.0
Poland Northeastern
(Białowieza
Primeval forest),
Southern
(Radomsko
forest)
Podsiadly
et al. (2011)
Prospective
cohort (2008–
2009)
Not described 129 Forestry workers
d
Not described Standard
two-tier
ELISA+WB
IgG
34.0
Poland Lublin Cisak et al.
(2008)
Cross-sectional
(1998–2007)
Not described 94 Farmers
d
Mean (SD):
56.3 (14.3)
Standard
two-tier
ELISA+WB
IgG and/or
IgM
32.9
50 Blood donors
b
Mean (SD):
29.7 (5.0)
Standard
two-tier
ELISA+WB
IgG and/or
IgM
6.0
Poland National
c
Zaja˛c et al.
(2017)
Cross-sectional
(2015–2016)
Convenience 3597 Farmers
d
Mean (SD):
51.3 (11.4)
Single tier ELISA IgM 11.5
ELISA IgG 13.7
Gostynin 150 Single tier ELISA IgM 13.3
Gostynin 150 Single tier ELISA IgG 14.7
Siedlce 329 Single tier ELISA IgM 10.3
Siedlce 329 Single tier ELISA IgG 16.7
Kolno 120 Single tier ELISA IgG 14.2
Kolno 120 Single tier ELISA IgM 6.7
Siemiatycze 106 Single tier ELISA IgM 10.4
Siemiatycze 106 Single tier ELISA IgG 19.8
Biała Podlaska 120 Single tier ELISA IgM 14.2
Biłgoraj 59 Single tier ELISA IgM 11.9
Chełm 120 Single tier ELISA IgM 8.3
Kras
´nik 317 Single tier ELISA IgM 8.5
Puławy 103 Single tier ELISA IgM 9.7
Radzyn
´Podlaski 114 Single tier ELISA IgM 19.3
Włodawa 150 Single tier ELISA IgM 25.3
Zamos
´c
´99 Single tier ELISA IgM 8.1
We˛gro
´w 182 Single tier ELISA IgM 8.8
Hajno
´wka 103 Single tier ELISA IgM 20.4
Augusto
´w 150 Single tier ELISA IgM 6.0
Mon
´ki 99 Single tier ELISA IgM 7.1
Suwałki 135 Single tier ELISA IgM 12.6
(continued)
201
Table 1. (Continued)
Country
National or region
within country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Biała Podlaska 120 Single tier ELISA IgG 20.0
Biłgoraj 59 Single tier ELISA IgG 10.2
Chełm 120 Single tier ELISA IgG 5.8
Kras
´nik 317 Single tier ELISA IgG 11.4
Puławy 103 Single tier ELISA IgG 14.0
Radzyn
´Podlaski 114 Single tier ELISA IgG 16.7
Włodawa 150 Single tier ELISA IgG 24.0
Zamos
´c
´99 Single tier ELISA IgG 16.2
We˛gro
´w 182 Single tier ELISA IgG 13.7
Hajno
´wka 103 Single tier ELISA IgG 20.4
Augusto
´w 150 Single tier ELISA IgG 12.7
Mon
´ki 99 Single tier ELISA IgG 10.2
Suwałki 135 Single tier ELISA IgG 18.5
Poland Southern Poland Buczek et al.
(2009)
Cross-sectional
(2003–2006)
Convenience 291 Office workers
b
Not described Single tier ELISA IgM 10.0
ELISA IgG 13.7
864 Forestry workers
d
ELISA IgM 13.8
ELISA IgG 25.0
Gidle 216 Single tier ELISA IgM 6.0
Herby 203 Single tier ELISA IgM 4.9
Kłobuck 160 Single tier ELISA IgM 1.25
Koniecpol 211 Single tier ELISA IgM 6.2
Przedbo
´rz 141 Single tier ELISA IgM 6.4
Złoty Potok 224 Single tier ELISA IgM 17.4
Gidle 216 Single tier ELISA IgG 21.3
Herby 203 Single tier ELISA IgG 22.2
Kłobuck 160 Single tier ELISA IgG 20.6
Koniecpol 211 Single tier ELISA IgG 23.7
Przedbo
´rz 141 Single tier ELISA IgG 14.2
Złoty Potok 224 Single tier ELISA IgG 14.3
Poland Eleven forest
inspectorates
Kiewra et al.
(2018)
Cross-sectional
(2016)
Not described 646 Forestry workers
d
Range: 21–67 Standard
two-tier
ELISA+WB
IgM
8.6
Standard
two-tier
ELISA+WB
IgG
17.8
Bardo 49 Standard
two-tier
ELISA+WB
IgM
8.1
Legnica 51 Standard
two-tier
ELISA+WB
IgM
15.6
Milicz 89 Standard
two-tier
ELISA+WB
IgM
6.7
Henryko
´w 34 Standard
two-tier
ELISA+WB
IgM
2.9
Jugo
´w 59 Standard
two-tier
ELISA+WB
IgM
8.4
(continued)
202
Table 1. (Continued)
Country
National or region
within country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Oles
´nica 96 Standard
two-tier
ELISA+WB
IgM
12.5
Ruszo
´w 65 Standard
two-tier
ELISA+WB
IgM
6.1
S
´nie_
zka 48 Standard
two-tier
ELISA+WB
IgM
8.3
S
´wierado
´w 55 Standard
two-tier
ELISA+WB
IgM
9.0
S
´wie˛toszo
´w 37 Standard
two-tier
ELISA+WB
IgM
2.7
Woło
´w 63 Standard
two-tier
ELISA+WB
IgM
9.5
Bardo 49 Standard
two-tier
ELISA+WB
IgG
24.4
Legnica 51 Standard
two-tier
ELISA+WB
IgG
19.6
Milicz 89 Standard
two-tier
ELISA+WB
IgG
12.3
Jugo
´w 59 Standard
two-tier
ELISA+WB
IgG
22.0
Oles
´nica 96 Standard
two-tier
ELISA+WB
IgG
16.6
Ruszo
´w 65 Standard
two-tier
ELISA+WB
IgG
15.3
S
´nie_
zka 48 Standard
two-tier
ELISA+WB
IgG
27.0
S
´wierado
´w 55 Standard
two-tier
ELISA+WB
IgG
16.3
S
´wie˛toszo
´w 37 Standard
two-tier
ELISA+WB
IgG
10.8
Woło
´w 63 Standard
two-tier
ELISA+WB
IgG
11.1
Poland Lublin Province Pan
´czuk et al.
(2019)
Cross-sectional
(N/A)
Not described 150 Hunters and
occupationally
exposed persons
(agriculture,
collecting
groundcover
fruits,
recreational
activity in
forested areas)
d
Range: 17–80 Standard
two-tier
ELISA IgG
VlsE+WB
IgG and/or
IgM
38.0
Standard
two-tier
ELISA IgG
VlsE+WB
IgG
36.7
Standard
two-tier
ELISA IgG
VlsE+WB
IgM
2.7
(continued)
203
Table 1. (Continued)
Country
National or region
within country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Russia Northeastern
Siberia (Sakha
Republic)
Magnaval
et al. (2016)
Cross-sectional
(2012)
Random 77 Healthy
volunteers
b
‡18 Single tier ELISA IgG 10.3
WB IgG 1.6
Slovakia Eastern Slovakia Za
´kutna
´et al.
(2015b)
Cross-sectional
(2011)
Convenience 124 Blood donors
b
‡30 Single tier ELISA IgG 15.3
WB IgG 1.6
Slovakia Eastern Slovakia Za
´kutna
´et al.
(2015a)
Cross-sectional
(2011–2012)
Convenience 193 Agriculture and
forestry
workers
d
‡30 Single tier ELISA IgG 29.2
36 Police and border
customs agents
d
Single tier ELISA IgG 11.1
48 Persons frequently
staying in the
countryside
d
Single tier ELISA IgG 20.8
Slovakia Senec and Senica
districts
Bazovska
´et al.
(2010)
Cross-sectional
(2008–2009)
Not described 302 Blood donors
b
Not described Single tier ELISA
IgG+WB
IgG VlsE
8.6
Slovakia Eastern Slovakia Bus
ˇova
´et al.
(2018)
Cross-sectional
(2013–2016)
Not described 135 Gardeners and
soldiers working
with
occupational
exposure to
ticks
d
Mean (SD):
35.76
(11.17)
Single tier ELISA IgG 15.6
ELISA IgM 5.9
Slovakia Slovakia Bazovska et al.
(2005)
Cross-sectional
(1987–2004)
Not described 250 Blood donors
b
Not described Standard
two-tier
ELISA+WB
IgG and/or
IgM
12.8
Slovenia Five
establishments
of the Slovenian
Forest Service
Rojko et al.
(2005)
Cross-sectional
(March to
November
2002)
Random 112 Forestry workers
d
Median
(range): 40
(22–62)
Single tier ELISA IgG 25.8
ELISA IgM 16.4
IFA 9.8
93 Indoor workers
from the same
region
b
Median
(range): 42
(23–65)
Single tier ELISA IgG 9.7
ELISA IgM 16.2
IFA 4.3
Ukraine National
b
Biletska et al.
(2008)
Cross-sectional
(2003–2006)
Not described 2393 Healthy people
b
Not described Single tier IFA IgG+IgM 34.3
Ukrainian Polissya 567 Single tier IFA IgG+IgM 32.6
Forest steppe 498 Single tier IFA IgG+IgM 35.3
Steppe 967 Single tier IFA IgG+IgM 38.2
Carpathian region 361 Single tier IFA IgG+IgM 25.2
a
Includes single-tier test results and two-tier overall test results based on a standard or modified algorithm (Branda and Steere 2021, Marques et al. 2021).
b
General population.
c
Nationally representative general population.
d
High-risk population.
ELISA, enzyme-linked immunoassay; IgG, immunoglobulin G; IgM, immunoglobulin M; IFA, immunofluorescence assay; N/A, not available; SD, standard deviation; SP, seroprevalence; VlsE,
variable major protein-like sequence, expressed; WB, Western blot.
204
Table 2. Estimates of Lyme Borreliosis Seroprevalence in Northern Europe from Published Literature, 2005–2020
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic test
Final SP
result, %
a
Baltic States
Estonia Saaremaa Parm et al.
(2015)
Cross-sectional
(2012)
Cluster
b
184 Hunters
c
Median (IQR):
41 (29–50)
Single tier ELISA IgG 46.7
Single tier ELISA IgM 1.0
Single tier ELISA IgM+IgG 7.0
Lithuania National
d
Motiejunas
et al. (1994)
Cross-sectional
(1988)
Random 268 Foresters
c
Not described Single tier IFA IgG 14.0
115 Field workers
c
Single tier IFA IgG 22.0
68 Veterinarians
c
Single tier IFA IgG 32.0
Scandinavia
Finland National
d
Cuellar et al.
(2020)
Cross-sectional
(1968–1972)
Convenience 994 General
population
e
Median (range):
57 (15–86)
Modified
two-tier
f
Whole-cell
sonicate IgG+C6
Lyme ELISA+
RecomBead IgG
20.0
Finland National
d
van Beek et al.
(2018)
Cross-sectional
(2011)
Cluster 2000 General
population
e
‡29 Modified
two-tier
g
Whole-cell
sonicate IgG+C6
Lyme ELISA+
RecomBead IgG
4.3
Norway Sogn and
Fjordane
Hjetland et al.
(2014)
Cross-sectional
(2010)
Convenience 1213 Blood donors
e
Mean (range):
45.8 (19–69)
Standard
two-tier
ELISA IgG
VlsE+WB IgG
6.1
Standard
two-tier
ELISA IgG
VlsE+WB IgM
2.8
Standard
two-tier
ELISA IgM
VlsE+WB IgM
4.9
Standard
two-tier
C6 ELISA+WB
IgG
5.8
Standard
two-tier
C6 ELISA+WB
IgM
2.3
Norway National
d
Vestrheim et al.
(2016)
Cross-sectional
(2011–2013)
Not described 3057 Residual sera
(pertussis
study)
e
‡2 Single tier ELISA IgG VlsE 2.7
Single tier EIA IgG 3.4
Akershus 601 Single tier ELISA IgG VlsE 2.0
Akershus 601 Single tier EIA IgG 1.8
Oslo 547 Single tier ELISA IgG VlsE 4.0
Oslo 547 Single tier EIA IgG 3.5
Telemark 178 Single tier ELISA IgG VlsE 3.9
Telemark 178 Single tier EIA IgG 4.5
Vest-Agder 198 Single tier ELISA IgG VlsE 7.6
Vest-Agder 198 Single tier EIA IgG 9.6
Hordaland 499 Single tier ELISA IgG VlsE 2.4
Hordaland 499 Single tier EIA IgG 3.8
(continued)
205
Table 2. (Continued)
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic test
Final SP
result, %
a
Sogn og
Fjordane
120 Single tier ELISA IgG VlsE 2.5
Sogn og
Fjordane
120 Single tier EIA IgG 4.2
Hedmark 194 Single tier ELISA IgG VlsE 1.5
Hedmark 194 Single tier EIA IgG 1.0
Nordland 239 Single tier ELISA IgG VlsE 0.8
Nordland 239 Single tier EIA IgG 2.1
Troms 180 Single tier ELISA IgG VlsE 0
Troms 180 Single tier EIA IgG 1.1
Sør-Trøndelag 301 Single tier ELISA IgG VlsE 2.7
Sør-Trøndelag 301 Single tier EIA IgG 2.7
Norway Søgne Thortveit et al.
(2020)
Cross-sectional
(2015–2016)
Consecutive 2968 General
population
e
Range: 18–69 Single tier ELISA IgG 22.9
Sweden Kalmar County Carlsson et al.
(2018)
Cross-sectional
(2012–2013)
Consecutive 873 Blood donors
with no LB
history
e
Median (range):
45 (18–72)
Single tier
Single tier
IFA IgG ( ‡8)
IFA IgG ( ‡12)
11.0
8.0
115 Blood donors
with unknown
history of LB
e
Median (range):
48 (18–68)
Single tier IFA IgG ( ‡8) 17.0
Sweden Kalmar County Johansson et al.
(2017)
Cross-sectional
(2011/2014)
Consecutive 573 Blood donors
e
Range: 18–69 Single tier C6 ELISA IgG
and/or IgM
23.2
Scotland Edinburgh,
Southeast
Scotland,
West of
Scotland
Munro et al.
(2015)
Cross-sectional
(2010–2011)
Convenience 1440 Blood donors Not described Standard
two-tier
ELISA IgG and/or
IgM+WB IgG
4.2
a
Includes single-tier test results and two-tier overall test results based on a standard or modified algorithm (Branda and Steere 2021, Marques et al. 2021).
b
Cluster sampling: methodology that involves (1) dividing the population into subgroups or clusters that are not necessarily (and preferably not) homogeneous, (2) drawing a random sample of the
clusters, and (3) selecting all or a random sample of persons in each cluster.
c
High-risk population.
d
Nationally representative general population.
e
General population.
f
Sample taken *50 years ago and then tested with current diagnostic test.
g
Modified based on current guidelines for articles published after modified testing strategies were published (Branda and Steere 2021).
C6, C6 protein of the variable major protein-like sequence lipoprotein; EIA, enzyme immunoassay; IQR, interquartile range; LB, Lyme borreliosis.
206
Table 3. Estimates of Lyme Borreliosis Seroprevalence in Southern Europe from Published Literature, 2005–2020
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic test
Final SP
result, %
a
Italy Arezzo, Florence,
and Siena
Tomao et al.
(2005)
Prospective
cohort (1999–
2001)
Not described 365 Blood donors
b
Mean (SD):
43.36 (8.16)
Standard
two-tier
c
ELISA+WB IgG
and/or IgM
3.5
Standard
two-tier
d
ELISA+WB IgG
and/or IgM
1.6
412 Forestry workers
e
Mean (SD):
43.71 (11.13)
Standard
two-tier
c
ELISA+WB IgG
and/or IgM
7.0
Standard
two-tier
d
ELISA+WB IgG
and/or IgM
3.8
Italy Lazio region Di Renzi et al.
(2010)
Prospective
cohort (2008)
Not described 145 Forestry rangers
e
Mean (SD):
41.0 (7.8)
Standard
two-tier
ELISA+WB IgG 0.68
Standard
two-tier
ELISA+WB IgM 13.1
282 Blood donors
b
Mean (SD):
40.4 (9.7)
Standard
two-tier
ELISA+WB IgG 1.1
Standard
two-tier
ELISA+WB IgM 8.2
Serbia Belgrade Jovanovic et al.
(2015)
Prospective
cohort (2014)
Convenience 34 Forestry workers
e
Range: 25–45 Standard
two-tier
ELISA+WB IgM
and/or IgG
11.8
35 Blood donors
b
Standard
two-tier
ELISA+WB IgM
and/or IgG
8.6
Serbia Belgrade Krstic
´and
Stajkovic
´
(2007)
Cross-sectional
(2005)
Cluster 34 Occupationally
exposed to
ticks (public
utility
workers)
e
Not described Single tier ELISA IgG and/
or IgM
23.5
35 Not
occupationally
exposed to
ticks (military
medical
cadets)
b
Single tier ELISA IgG and/
or IgM
2.9
Spain Guadalajara
province
Lledo et al.
(2019)
Cross-sectional
(2019)
Not described 100 Occupationally
exposed to
ticks (forestry,
agriculture,
cattle raising)
e
Median (IQR):
33 (29.5–
40.25)
Single tier IFA IgG 7.0
Spain Asturias Barreiro-Hurle
et al. (2020)
Cross-sectional
(2014)
Convenience 316 Blood donors
b
Mean (SD):
46 (8.5)
Standard
two-tier
ELISA+WB IgG 5.1
432 Outpatients
without
infectious
disease
b
Mean (SD):
54 (14.1)
Standard
two-tier
ELISA+WB IgG 14.4
(continued)
207
Table 3. (Continued)
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic test
Final SP
result, %
a
Spain Navarra Oteiza-Olaso
et al. (2011)
Cross-sectional
(1996)
Random 1429 Residents of
Navarra
b
‡15 Single tier ELISA C6 4.4
Stockbreeders 13.2
Farmers 3.5
Turkey Erzurum Center
and Pasinler
district
Uyanık et al.
(2009)
Prospective
cohort (2007–
2008)
Convenience 101 Residents with a
high risk of
tick exposure
living in a
high-risk area
(Erzurum
Province)
e
Male mean:
39.5; female
mean: 33.7
Modified
two-tier
f
ELISA+ELFA
IgG
2.0
79 Blood donors
with low risk
of exposure to
ticks
b
Male mean:
37.9; female
mean: 35.8
Modified
two-tier
f
ELISA+ELFA
IgG
2.5
Turkey Du
¨zce Kaya et al.
(2008)
Prospective
cohort (2007)
Convenience 349 Forestry workers
e
Median (range):
46.9 (14–92)
Standard
two-tier
ELISA+WB IgG 1.1
193 Blood donors
b
‡10 Standard
two-tier
ELISA+WB IgG 0.0
Turkey Du
¨zce Akar et al.
(2019)
Cross-sectional
(2016)
Convenience 193 Residents of a
high-risk area
(Duzce)
e
Mean (SD):
47.4 (13.5)
Standard
two-tier
ELISA+WB IgM 1.5
Standard
two-tier
ELISA+WB IgG 6.2
Turkey Van region Parlak et al.
(2015)
Cross-sectional
(2012)
Cluster (random
sampling in
clusters)
446 Residents of a
high-risk area
(Van region)
e
Mean (SD):
39.6 (15.5)
Standard
two-tier
ELISA+WB IgG 0.9
Turkey Tekkekoy district Aslan Basxbulut
et al. (2012)
Cross-sectional
(2006)
Cluster (random
sampling in
clusters)
419 Tekkeko
¨y (high
tick
population)
e
Mean (SD):
33.07 (19.58)
Standard
two-tier
ELISA+WB IgG 3.3
Turkey Province of Bolu Bucak et al.
(2016)
Cross-sectional
(August to
October
2013)
Stratified
random
196 Residents of
Bolu
b
Adults and
children
Standard
two-tier
ELISA+WB IgG
and/or IgM
8.1
Turkey Erzincan Cikman et al.
(2019)
Cross-sectional
(2014)
Cluster 368 Residents of
Erzincan (high
tick
population)
e
Mean (SD):
51.43 (16.91)
Standard
two-tier
ELISA+WB IgG 2.1
Turkey Sivas region Gu
¨nesxet al.
(2005)
Cross-sectional
(2005)
Random 270 Persons with
contact with
livestock
e
Mean (range):
38.2 (13–80)
Single tier ELISA IgG 0.4
135 Healthy controls
b
Single tier ELISA IgG 0.7
Turkey Van region Bozkurt et al.
(2008)
Prospective
cohort (2008)
Random 460 Residents of the
Van region
b
Single tier EIA IgM 5.8
EIA IgG 1.5
O
¨zalp 31 Single tier EIA IgG 6.5
(continued)
208
Table 3. (Continued)
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic test
Final SP
result, %
a
Gevaf 14 Single tier EIA IgG 7.1
Muradiye 29 Single tier EIA IgG 3.4
Van 185 Single tier EIA IgG 1.6
Ozalp 31 Single tier EIA IgM 19.4
Cxaldran 32 Single tier EIA IgM 18.8
Baflkale 30 Single tier EIA IgM 10.0
Edremit 11 Single tier EIA IgM 9.1
Gevaf 14 Single tier EIA IgM 7.1
Muradiye 29 Single tier EIA IgM 6.9
Van 185 Single tier EIA IgM 3.8
Ercis 77 Single tier EIA IgM 1.3
Turkey Trabzon city and
counties
Cora et al.
(2017)
Retrospective,
cross-
sectional
(2007–2008)
Convenience 884 Residents of
Trabzon
Range: 20–79 Standard
two-tier
ELISA+WB IgG 14.5
555 Occupationally
exposed to
ticks
e
Standard
two-tier
ELISA+WB IgG 15.8
329 Not
occupationally
exposed to
ticks
b
Standard
two-tier
ELISA+WB IgG 12.2
Akc¸aabat 95 Standard
two-tier
ELISA+WB IgG 4.2
Araklı 49 Standard
two-tier
ELISA+WB IgG 22.4
Cxaykara 6 Standard
two-tier
ELISA+WB IgG 50
Du
¨zko
¨y 12 Standard
two-tier
ELISA+WB IgG 0
Mac¸ka 22 Standard
two-tier
ELISA+WB IgG 9.1
Of 48 Standard
two-tier
ELISA+WB IgG 14.6
Su
¨rmene 37 Standard
two-tier
ELISA+WB IgG 13.5
Vakfıkebir 44 Standard
two-tier
ELISA+WB IgG 22.7
Yomra 30 Standard
two-tier
ELISA+WB IgG 26.7
Turkey Manisa Gazi et al.
(2016)
Cross-sectional
(2012)
Random 324 Farmers Mean (SD):
49.16 (16.78)
Single tier IFA IgG VlsE 4.3
a
Includes single test results and two-tier overall test results based on a standard or modified algorithm (Branda and Steere 2021, Marques et al. 2021).
b
General population.
c
According to manufacturer’s instructions.
d
According to CDC-recommended criteria.
e
High-risk population.
f
Modified based on current guidelines for articles published after modified testing strategies were published (Branda and Steere 2021).
CDC, Centers for Disease Control and Prevention; ELFA, enzyme-linked fluorescent assay.
209
Table 4. Estimates of Lyme Borreliosis Seroprevalence in Western Europe from Published Literature, 2005–2020
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Austria Districts of
Burgenland
Cetin et al.
(2006)
Cross-sectional
(2002–2003)
Convenience 1253 Hunters
b
Mean (SD):
51 (13)
Standard
two-tier
ELISA+WB IgG 53.7
Austria National
c
Sonnleitner
et al. (2015)
Cross-sectional
(2009)
Not described 1607 Blood donors
d
‡18 Standard
two-tier
ELISA+WB IgG 5.2
Lech Valley 58 Standard
two-tier
ELISA+WB IgG 9.0
Upper Inn Valley 120 Standard
two-tier
ELISA+WB IgG 3.0
Central Inn
Valley
411 Standard
two-tier
ELISA+WB IgG 6.0
Lower Inn Valley 317 Standard
two-tier
ELISA+WB IgG 10.0
East Tyrol 104 Standard
two-tier
ELISA+WB IgG 7.0
Pustertal 95 Standard
two-tier
ELISA+WB IgG 1.0
Eisack Valley 79 Standard
two-tier
ELISA+WB IgG 0
Upper Eisack
Valley
277 Standard
two-tier
ELISA+WB IgG 2.0
Lower Eisack
Valley
144 Standard
two-tier
ELISA+WB IgG 2.0
Belgium Wallonia De Keukeleire
et al. (2016)
Cross-sectional
(2011)
Convenience 31 Farmers
b
Veterinarians
b
Single tier ELISA IgG 9.7
96 Single tier ELISA IgG 4.1
Hainaut 26 Single tier ELISA IgG 11.5
Leige 37 Single tier ELISA IgG 8.1
Luxemburg 26 Single tier ELISA IgG 3.9
Belgium Wallonia De Keukeleire
et al. (2018)
Cross-sectional
(2000–2013)
Convenience 310 Forestry
workers
b
Mean (range):
49 (24–65)
Single tier ELISA IgG 21.6
Namur 50 Single tier ELISA IgG 34.0
Arlon 24 Single tier ELISA IgG 29.0
Malmedy 42 Single tier ELISA IgG 14.0
Neufcha
ˆteau 44 Single tier ELISA IgG 14.0
Belgium National
c
Lernout et al.
(2019)
Cross-sectional
(2013–2015)
Convenience 3215 Serum bank
samples
All ages Standard
two-tier
CLIA IgG+WB
IgG
1.1
Region
Brussels 378 Standard
two-tier
CLIA IgG+WB
IgG
1.0
Flanders 2052 Standard
two-tier
CLIA IgG+WB
IgG
1.3
(continued)
210
Table 4. (Continued)
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Wallonia 785 Standard
two-tier
CLIA IgG+WB
IgG
0.7
Provinces
West Flanders 522 Standard
two-tier
CLIA IgG+WB
IgG
0.3
East Flanders 431 Standard
two-tier
CLIA IgG+WB
IgG
0.4
Flemish
Brabant
532 Standard
two-tier
CLIA IgG+WB
IgG
1.5
Antwerp 551 Standard
two-tier
CLIA IgG+WB
IgG
1.2
Limburg 394 Standard
two-tier
CLIA IgG+WB
IgG
3.0
Hainaut 298 Standard
two-tier
CLIA IgG+WB
IgG
0
Walloon
Brabant
69 Standard
two-tier
CLIA IgG+WB
IgG
2.8
Lie
`ge 175 Standard
two-tier
CLIA IgG+WB
IgG
1.7
Namur 62 Standard
two-tier
CLIA IgG+WB
IgG
0
Luxembourg 181 Standard
two-tier
CLIA IgG+WB
IgG
0.5
France National
c
Thorin et al.
(2008)
Cross-sectional
(2002–2003)
Convenience 2975 Forestry field
professionals
b
Range: 17–81 Standard
two-tier
ELISA+WB IgG
and/or IgM
14.1
Alsace 636 Standard
two-tier
ELISA+WB IgG
and/or IgM
26.9
Lorraine 885 Standard
two-tier
ELISA+WB IgG
and/or IgM
16.5
Champagne-
Ardenne
485 Standard
two-tier
ELISA+WB IgG
and/or IgM
8.2
Burgundy 400 Standard
two-tier
ELISA+WB IgG
and/or IgM
7.5
Franche-Comte
´554 Standard
two-tier
ELISA+WB IgG
and/or IgM
5.6
France Southwestern
France
Ruiz et al.
(2020)
Cohort study
(2007–2016)
Random 689 Retired farmers ‡65 Standard
two-tier
ELISA IgG+WB
IgG
6.5
(continued)
211
Table 4. (Continued)
Country
National or
region within
country References
Study design
(data collection
period)
Sampling
method
Sample
size, N
Cohort
description
Age group,
years
Diagnostic
testing
strategy
Type of
diagnostic
test
Final SP
result, %
a
Germany National
c
Wilking et al.
(2015)
Cross-sectional
(2008–2011)
Not described 6945 General
population
d
‡18 Standard
two-tier
ELISA+WB IgG 10.6
Middle states 3087 Standard
two-tier
ELISA+WB IgG 9.8
Western states 4748 Standard
two-tier
ELISA+WB IgG 10.1
Eastern states 2197 Standard
two-tier
ELISA+WB IgG 11.6
Northern states 1767 Standard
two-tier
ELISA+WB IgG 10.2
Germany National
c
Dehnert et al.
(2012)
Cross-sectional
(2003–2006)
Not described 12,614 Volunteers
d
1–17 Standard
two-tier
ELISA+WB IgG 3.6
West 8248 Standard
two-tier
ELISA+WB IgG 4.0
East 4272 Standard
two-tier
ELISA+WB IgG 4.2
North 3294 Standard
two-tier
ELISA+WB IgG 3.6
Central 5522 Standard
two-tier
ELISA+WB IgG 3.7
South 3704 Standard
two-tier
ELISA+WB IgG 5.1
Rural area 2745 Standard
two-tier
ELISA+WB IgG 5.1
Small town 3322 Standard
two-tier
ELISA+WB IgG 4.6
Mid-size town 3666 Standard
two-tier
ELISA+WB IgG 3.7
Metropolitan area 2787 Standard
two-tier
ELISA+WB IgG 3.0
Netherlands National
c
van Gorkom
et al. (2017)
Cross-sectional
(2013–2015)
Convenience 147 Healthy
individuals
d
Mean (IQR):
42.3 (28.0–
53.4)
Standard
two-tier
ELISA C6+WB
IgG and/or
IgM
13.6
a
Includes single-tier test results and two-tier overall test results based on a standard or modified algorithm (Branda and Steere 2021, Marques et al. 2021).
b
High-risk population.
c
Nationally representative general population.
d
General population.
CLIA, chemiluminescent immunoassay.
212
standard two-tier testing was 17.8% (ELISA+WB IgG) in
forestry workers in S
´wie˛toszo
´w, Poland (Kiewra et al. 2018)
and 38% (ELISA IgG VlsE+WB IgG and/or IgM) in hunt-
ers and occupationally exposed persons in Lublin Province,
Poland (Pan
´czuk et al. 2019). In studies with single-tier
testing, the seroprevalence in forestry workers was 25.8%
(ELISA IgG) in Slovenia (Rojko et al. 2005), 37.2% (ELISA
IgG+IgM) in Hungary (Lakos et al. 2012), and 29.2%
(ELISA IgG) in Slovakia.
Subnational seroprevalence. Subnational data from five
regions in Ukraine were available from a study that assessed
seroprevalence in healthy persons based on a single-tier
testing strategy (IFA IgM+IgG) (Table 1). Seroprevalence
ranged from 25.2% in the Carpathian region to 38.2% in the
Steppe and up to 70% in the local administrative district of
Kiverci in the region of Volyn Oblast (Biletska et al. 2008).
Northern Europe (Estonia, Finland, Lithuania, Norway,
Scotland, Sweden)
Seroprevalence among general populations. Seven arti-
cles reported LB seroprevalence in Finland, Norway, and
Sweden in the general population (Table 2) (Hjetland et al.
2014, Vestrheim et al. 2016, Johansson et al. 2017, Carlsson
et al. 2018, van Beek et al. 2018, Cuellar et al. 2020, Thortveit
et al. 2020), with testing based on samples from blood donors
and residual sera from clinical trials and population-based
surveys. General seroprevalence estimates were 6.1% (ELISA
IgG VlsE+WB IgG) and 5.8% (C6 ELISA+WB IgG) among
healthy blood donors in Norway (Hjetland et al. 2014).
Among the general population in Finland, LB seroprevalence
was 4.3% using modified two-tier testing (van Beek et al.
2018) versus 20% using a three-step testing method (as part
of a modified two-tier testing strategy) in serum samples
collected between 1968 and 1972 (Cuellar et al. 2020).
Seroprevalence in high-risk groups. Two studies of
high-risk groups that used single-tier testing strategies
(Motiejunas et al. 1994, Parm et al. 2015) reported sero-
prevalence estimates of 46.7% (ELISA IgG) in Estonian
hunters and 14–32% (IFA IgG) in Lithuanian forestry
workers, outdoor field workers, and veterinarians (Table 2).
Subnational seroprevalence. Five studies reported sero-
prevalence estimates from regions within Norway and
Sweden. In Norway, seroprevalence ranged from 0% to
22.9% using single-tier testing strategies and various testing
methods (Thortveit et al. 2020, Vestrheim et al. 2016)
(Table 2). In Sweden, LB seroprevalence in Kalmar County
in the southeast using single-tier testing (IFA IgG) was esti-
mated to be between 8% and 17% depending on the assay
cutoff employed and blood donor population studied
(Carlsson et al. 2018). One study (Munro et al. 2015) reported
a seroprevalence of 4.2% in blood donors by a standard two-
tier testing method in the regions of West of Scotland,
Edinburgh, and South East Scotland (Table 2).
Southern Europe (Italy, Serbia, Spain, Turkey)
Seroprevalence among general populations. Eighteen
articles reported seroprevalence of LB in four countries in
Southern Europe (Gu
¨nesxet al. 2005, Tomao et al. 2005,
Krstic
´and Stajkovic
´2007, Bozkurt et al. 2008, Kaya et al.
2008, Uyanık et al. 2009, Di Renzi et al. 2010, Oteiza-Olaso
et al. 2011, Aslan Basxbulut et al. 2012, Jovanovic et al. 2015,
Parlak et al. 2015, Bucak et al. 2016, Gazi et al. 2016, Cora
et al. 2017, Akar et al. 2019, Cikman et al. 2019, Lledo et al.
2019, Barreiro-Hurle et al. 2020). All studies reported sub-
national rather than country-wide estimates (Table 3); 15
reported seroprevalence in groups at high risk of tick expo-
sure based on occupation or residential area, and 11 reported
on populations at low risk.
Estimates of LB seroprevalence were <10% for the gen-
eral population in most regions of Italy, Serbia, Spain, and
Turkey. An exception to this, in Turkey, determined using
two-tier testing (ELISA+WB IgG), was an overall seropre-
valence of 14.5% in residents of the city and environs of
Trabzon, including Araklı (22.4%), Mac¸ka (9.1%), Of (14.6%),
Su
¨rmene (13.5%), Vakfıkebir (22.7%), and Yomra (26.7%)
(Cora et al. 2017). Furthermore, seroprevalence determined
using a single-tier strategy was reported to be 10.0–19.4% in
residents of three areas in the Van region (Ozalp, Cxaldran,
and Baflkaleup) (Bozkurt et al. 2008).
Seroprevalence in high-risk groups. In high-risk popula-
tions, LB seroprevalence was <1% using standard two-tier
testing (ELISA+WB IgG) both in forestry rangers in Lazio,
Italy (Di Renzi et al. 2010) and in residents of the Van region
of Turkey (Parlak et al. 2015), but was 23.5% in public utility
workers in Belgrade, Serbia (Krstic
´and Stajkovic
´2007). In
low-risk populations in Southern Europe, seroprevalence
using standard two-tier testing (measured by different
EIAs+WB IgG and/or IgM) ranged from <1% in Lazio, Italy
(Di Renzi et al. 2010) and the Du
¨zce, Van, Sivas, and Du
¨zko
¨y
regions of Turkey (Gu
¨nesxet al. 2005, Kaya et al. 2008, Parlak
et al. 2015, Cora et al. 2017) to 50% in Cxaykara, Turkey (Cora
et al. 2017).
Western Europe (Austria, Belgium, France, Germany, the
Netherlands)
Seroprevalence among general populations. Ten arti-
cles reported estimates of LB seroprevalence in countries in
Western Europe, as summarized in Table 4 (Cetin et al. 2006,
Thorin et al. 2008, Dehnert et al. 2012, Sonnleitner et al.
2015, Wilking et al. 2015, De Keukeleire et al. 2016, 2018,
van Gorkom et al. 2017, Lernout et al. 2019, Ruiz et al. 2020).
Six articles reported seroprevalence in the general population
and five reported seroprevalence in groups at high risk of
occupational tick exposure. The national seroprevalence of
LB in volunteers or blood donors was 3.6% (ELISA+WB
IgG) in Germany (Dehnert et al. 2012) and 1.1% (chemilu-
minescent immunoassay [CLIA] IgG+WB IgG) in Belgium
(Lernout et al. 2019) based on a two-tier testing strategy.
As observed in other parts of Europe, there was substantial
heterogeneity in seroprevalence of antibodies against Bbsl
within individual countries according to region and occupa-
tional exposure. In Austria, seroprevalence among blood
donors ranged from 0% in the Eisack Valley to 10% in the
Lower Inn Valley (ELISA+WB IgG) based on two-tier test-
ing (Sonnleitner et al. 2015).
Seroprevalence in high-risk groups. The seroprevalence
of LB in populations with high-risk occupations was 14.1%
among a nationally representative cohort of forestry field
professionals in France, and 53.7% among hunters in Austria
SEROPREVALENCE OF LYME BORRELIOSIS IN EUROPE 213
(ELISA+WB IgG), using two-tier testing (Cetin et al.
2006). In Wallonia, Belgium, seroprevalence estimates based
on single-tier testing (ELISA IgG) among farmers and vet-
erinarians was 11.54% in Hainaut and 9.68% in Wallonia
(De Keukeleire et al. 2016), whereas in forestry workers
it reached 34% in Namur and 21.6% in Wallonia (De
Keukeleire et al. 2018).
Seroprevalence estimates by European region and
diagnostic strategy
Eastern Europe. The weighted mean seroprevalence of
LB in Eastern Europe among studies that used (standard)
two-tier testing strategies in general populations was 11.1%
(Table 5). Five studies (Bazovska et al. 2005, Cisak et al.
2008, Tokarska-Rodak et al. 2014, Kuchynka et al. 2016,
Pan
´czuk et al. 2019) used the IgG and IgM standard two-tier
test; the weighted mean of the high-risk group was higher
(40.6%) than in the low-risk group (11.1%). Four of 23
studies (Podsiadly et al. 2011, Kocbach and Kocbach 2014,
Bura et al. 2018, Kiewra et al. 2018) measured IgG in high-
risk populations only, giving a weighted mean of 24.7%.
When stratified by single-tier testing (IgM and IgG), sero-
prevalence was higher in high-risk groups (37.2%) than low-
risk groups (34.7%). For IgG alone, it was 16.1% in high-risk
groups versus 12.6% in low-risk groups.
Northern Europe. The weighted mean seroprevalence of
LB in Northern Europe among studies that used (standard)
two-tier testing strategies in general populations was 4.2%
(Table 6). Additionally, two studies from Finland (van Beek
et al. 2018, Cuellar et al. 2020) used a modified algorithm in
low-risk groups, yielding a weighted mean seroprevalence of
9.5%. Different algorithms were evaluated in this region,
including one study in Norway (Hjetland et al. 2014) using a
standard two-tier test with a weighted mean of 4.7% in the
low-risk group. When stratified by single-tier testing, the
weighted mean seroprevalence for IgG was higher in high-
risk groups (26.9%) than low-risk groups (12.0%).
Southern Europe. The weighted mean seroprevalence of
LB in Southern Europe among studies that used (standard)
two-tier testing strategies in general populations (Tomao
et al. 2005, Kaya et al. 2008, Di Renzi et al. 2010, Aslan
Basxbulut et al. 2012, Jovanovic et al. 2015, Parlak et al. 2015,
Bucak et al. 2016, Cora et al. 2017, Akar et al. 2019, Cikman
et al. 2019, Barreiro-Hurle et al. 2020) was 3.9% (Table 7).
The standard IgM and IgG weighted mean seroprevalence
was 5.7% in high-risk groups versus 3.9% in low-risk groups.
For single-tier testing (IgG and IgM), the mean seropre-
valence was 8.9% in high-risk groups versus 4.4% in low-
risk groups (Gu
¨nesxet al. 2005, Krstic
´and Stajkovic
´2007,
Bozkurt et al. 2008, Oteiza-Olaso et al. 2011, Gazi et al. 2016,
Lledo et al. 2019).
Western Europe. The weighted mean seroprevalence of
LB in Western Europe among studies that used (standard)
two-tier testing strategies in general populations was 13.6%
(Dehnert et al. 2012, Sonnleitner et al. 2015, Wilking et al.
2015, Lernout et al. 2019) (Table 8). This was lower than the
mean seroprevalence of high-risk groups (14.1%) based on
one study in France (Thorin et al. 2008) and two studies that
assessed seroprevalence by two-tiered IgG testing (37%)
(Cetin et al. 2006, Ruiz et al. 2020). Two studies in Belgium
(De Keukeleire et al. 2016, 2018) that used single-tier IgG
testing in high-risk populations gave a weighted mean sero-
prevalence of 16.9%.
Seroprevalence estimates by age and sex
Overall Europe. Seroprevalence results stratified by age
group and sex are presented in Supplementary Table S1.
Table 5. Weighted Mean Lyme Borreliosis
Seroprevalence in Eastern Europe from Published
Literature, 2005–2020
Diagnostic
testing strategy
Antibody
type
Risk
group
Mean SP
(95% CI), %
Single tier IgG+IgM Low risk 34.7 (32.8–36.6)
IgG 12.5 (9.4–16.7)
IgM 10.7 (7.3–15.2)
IgG+IgM High risk 37.2 (35.2–39.2)
IgG 16.1 (14.3–18.1)
IgM 12.6 (11.3–14.2)
Standard
two-tier
IgG+IgM Low risk 11.1 (7.1–17.2)
IgG+IgM High risk 40.6 (33.6–48)
IgG 24.7 (20.6–29.2)
IgM 7.6 (5.6–10.3)
CI, confidence interval.
Table 6. Weighted Mean Lyme Borreliosis
Seroprevalence in Northern Europe
from Published Literature, 2005–2020
Diagnostic
testing strategy
Antibody
type
Exposure
group
Mean SP
(95% CI), %
Single tier IgG+IgM Low risk 23.2 (20.3–26.3)
IgG 12.0 (10.9–13.2)
IgG+IgM High risk 7.1 (4.2–11.0)
IgG 26.9 (21.6–2.9)
IgM 1.1 (0.2–3.4)
Standard
two-tier
IgG+IgM Low risk 4.2 (3.3–5.5)
IgG 4.7 (3.8–5.8)
IgM 3.8 (3.0–4.9)
Modified
two-tier
IgG Low risk 9.5 (8.3–10.8)
Table 7. Weighted Mean Lyme Borreliosis
Seroprevalence in Southern Europe
from Published Literature, 2005–2020
Diagnostic
testing strategy
Antibody
type
Exposure
group
Mean SP
(95% CI), %
Single tier IgG+IgM Low risk 4.4 (3.5–5.7)
IgG 1.3 (0.6–3.0)
IgM 5.9 (4.1–8.0)
IgG+IgM High risk 8.5 (7.3–10.0)
IgG 3.2 (1.7–5.6)
Standard
two-tier
IgG+IgM Low risk 3.9 (2.2–6.6)
IgG 10.2 (8.3–12.6)
IgM 8.2 (5.6–11.4)
IgG+IgM High risk 5.7 (3.8–8.3)
IgG 5.3 (4.0–7.3)
IgM 6.5 (4.0–10.3)
Modified
two-tier
IgG Low risk 2.5 (0.4–7.8)
IgG High risk 2.0 (0.3–6.1)
214 BURN ET AL.
Age. Thirteen studies reported age-stratified LB seropre-
valence; all observed increasing seroprevalence for anti-
bodies against Bbsl with age. In adults, a seroprevalence of
at least 20% was observed in older age groups: ‡50 years
of age in Finland (Cuellar et al. 2020), ‡55 years of age in
France (Thorin et al. 2008), ‡60 years of age in Norway and
Turkey (Hjetland et al. 2014, Cora et al. 2017), and ‡70
years of age in Germany and Poland (Wilking et al. 2015,
Zaja˛c et al. 2017). The highest seroprevalence was observed
in Austrian hunters, in whom 59.3% of 50- to 59-year-olds
and 83.3% of >70-year-olds were seropositive (Cetin et al.
2006).
One study reported seroprevalence rates by age group in
children ‡2 years of age using sera collected during a per-
tussis vaccine study in Norway. The seroprevalence (single
tier, IgG) was 3.6% in 2- to 4-year-olds, 4.1% in 5- to 9-year-
olds, and 2.1% in 10- to 19-year-olds versus 3.7% in 20- to
39-year-olds and 6.0% in >50-year-olds (Vestrheim et al.
2016).
Sex. In 17 studies that reported seroprevalence by sex,
there was a trend toward higher seroprevalence in men
than women (Supplementary Table S1) regardless of risk
cohort.
Among high-risk groups in Estonia, seroprevalence (ELISA
IgG) in male hunters was 52.6% versus 18.7% in female
hunters (ELISA IgG) (Parm et al. 2015). The seroprevalence
estimate was 6.4% in male Belgian farmers and veterinarians
versus 0.0% in women (ELISA IgG) (De Keukeleire et al.
2018), 16.5% in male Polish farmers versus 11.7% in women
(ELISA IgG) (Zaja˛ c et al. 2017), and 14.3% in male forest
and field professionals in France versus 3.4% in women
(ELISA+WB IgG and/or IgM) (Thorin et al. 2008).
Similar trends were observed in low-risk groups in most
countries. In Spain and Norway, the seroprevalence estimates
were 6.5% (ELISA+WB IgG) and 13.0% (ELISA IgG VlsE)
in male blood donors versus 5.5% and 3.1% in female blood
donors, respectively (Hjetland et al. 2014, Barreiro-Hurle
et al. 2020). The seroprevalence in the general population
of Germany was 15.0% in men and 6.6% in women
(ELISA+WB IgG) (Wilking et al. 2015). In contrast, the
trend was reversed in Turkey and the United Kingdom, where
seroprevalence was consistently higher in women than in
men. While one study reported a seroprevalence of 6.1%
in male residents of a high-risk area versus 2.5% in women
(ELISA+ELFA [enzyme-linked fluorescent assay] IgG)
(Uyanık et al. 2009), six other studies of residents in high-risk
areas reported higher seroprevalence in women, with a dif-
ference between sexes of 0.2% to 6.0% (Aslan Basxbulut et al.
2012, Parlak et al. 2015, Bucak et al. 2016, Cora et al. 2017,
Akar et al. 2019, Cikman et al. 2019).
None of the studies showed a statistically significant dif-
ference between sex, except for one study in high-risk resi-
dents in Turkey, including ELISA and WB test results
showing more statistically significant ( p<0.05) greater
positive results in females (5.2%) than males (0.7%; ELISA
IgG) (Parlak et al. 2015).
Seroprevalence estimates by risk groups. The high
heterogeneity of the data (I
2
>90%, even after subanalyses by
diagnostic methods and strategies, age, and sex) prevented a
meta-analysis, but we did explore analysis by risk group.
Among studies that analyzed persons with greater risk for tick
exposure, LB seroprevalence (using standard two-tier for
IgG+IgM) was higher among these groups than in the gen-
eral population. While the difference in Eastern Europe was
statistically significant (40.6% [33.6–48.0%] vs. 11.1% [7.1–
17.2%] (Supplementary Table S5) where the two 95% CI did
not overlap), in Southern Europe and Western Europe, we
observed higher LB seroprevalence in high-risk group
compared with low-risk group but this difference was not
statistically significant (95% CI overlapped).
There were 12 studies that allowed calculation of ORs
to evaluate whether tick exposure risk group was associated
with seroprevalence (Supplementary Tables S2 and S3) by
comparison with populations at low risk of exposure to
ticks. Seven reported that the odds of LB seropositivity were
statistically significantly increased by 2- to 21-fold in high-
risk populations, suggesting that high-risk groups, including
forestry workers and rural residents and workers, share a
greater risk of seropositivity compared with low-risk popu-
lations. However, CIs were wide for many of the estimates.
Discussion
This review provides a comprehensive overview of the
seroprevalence of LB in Europe. The main finding of our
analysis is that LB is a disease of place (local setting) and
activity (both occupational and leisure). National-level sero-
prevalence estimates may ignore potentially much higher
subnational disease burdens, and conversely, subnational
higher-risk areas do not necessarily indicate high national
disease burden. Overall, LB seroprevalence estimates ranged
from 0% to 70% (the latter in an administrative region in the
Ukraine) (Biletska et al. 2008). There was a general trend
toward higher seroprevalence for general population data in
Western Europe and Eastern Europe, but on closer inspec-
tion there was substantial variation within the countries in
Southern and Northern Europe; this may also be due to dif-
ferences in Bbsl genospecies and I. ricinus abundance and
distribution (Strnad et al. 2017, Van den Wijngaard et al.
2017, Estrada-Pena et al. 2018).
LB seroprevalence trended higher, although inconsis-
tently, in persons undertaking at-risk occupational or leisure
activities in some studies, with the highest estimate (83.3%)
among hunters >70 years of age in Austria (Cetin et al. 2006)
The seroprevalence in people with higher exposure to ticks
was higher among these groups than in the general population
(40.6% vs. 3.9%); the same occurs in a systematic review in
human population where the high-risk population shows a
Table 8. Weighted Mean Lyme Borreliosis
Seroprevalence in Western Europe
from Published Literature, 2005–2020
Diagnostic
testing strategy
Antibody
type
Exposure
group
Mean SP
(95% CI), %
Single tier IgG High risk 16.9 (13.1–22.0)
Standard
two-tier
IgG+IgM Low risk 13.6 (9.2–19.1)
IgG 5.4 (5.0–5.8)
IgG+IgM High risk 14.1 (13.0–15.2)
IgG 37.0 (34.9–39.1)
SEROPREVALENCE OF LYME BORRELIOSIS IN EUROPE 215
seroprevalence of 18.8% (95% CI 10.1–29.4%) compared
with a much lower seroprevalence in the general population
of 5.7% (95% CI 4.3–7.3%) (Dong et al. 2022).
A 15-study meta-analysis reported that the OR for ser-
oprevalence was 1.9 (95% CI: 1.2–3.2) worldwide in outdoor
workers compared with controls (Magnavita et al. 2022). In-
terestingly, the risk changed over time and apparently de-
creased after 2010, possibly due to better education and/or
occupational protection, but this trend was not consistently
observed herein. A recent systematic review of global ser-
oprevalence data and characteristics of B. burgdorferi in hu-
man populations (Dong et al. 2022) estimated seroprevalence
to be 20.7% in Central Europe and 13.5% in Western Europe.
That review used a longer search time frame (1999–2021),
whereas we captured additional studies in Europe and were
ultimately more comprehensive. We also present diagnostic
testing methods and strategies used, as well as our calcu-
lations of final two-tier test results, to enhance the inter-
pretation of seroprevalence results while considering the
limitations of single-tier testing (e.g., more false positives).
The review by Dong and colleagues was also limited by
including population cohorts suspected to have LB, which
we excluded herein to reduce selection bias in seropreval-
ence estimates and ensure that we captured estimates in
populations without existing LB.
We found that LB seroprevalence increased with age,
reflecting both the cumulative risk of exposure to an infec-
ted tick over time and the persistence of antibodies to Bbsl,
which show varying and unpredictable kinetics but may
persist for years or even decades after acute infection
(Kalish et al. 2001, Peltomaa et al. 2003, Glatz et al. 2006).
Among 61 studies, only one study demonstrated statistically
significant differences between sexes, with higher positive
results in females in a high-risk region of Turkey (Parlak
et al. 2015).
A key data gap in the epidemiology of LB is the true
percentage of infections that are symptomatic versus asymp-
tomatic. This information is needed to compare the number of
symptomatic LB cases derived from seroprevalence data with
the number of surveillance-reported LB cases to estimate the
under-ascertainment of symptomatic LB cases by public
health surveillance. However, the proportion of asymptom-
atic infections is difficult to estimate given the lack of pros-
pective studies measuring the incidence of LB.
Nevertheless, three studies in Europe have estimated the
proportion of asymptomatic infected persons by measuring
seroconversion following a tick bite and the development of
clinical signs and symptoms of LB. The median proportion of
asymptomatic infected persons from these studies was 50%
(Hofhuis et al. 2013, Wilhelmsson et al. 2016, Markowicz
et al. 2021). A large, placebo-controlled study of a Lyme
vaccine in the United States tested blood samples in intervals
of months after vaccination. In this population, asymptomatic
Bbsl infections were recorded in 11% of participants over the
study period, which dropped to 7% when adjusted for those
who met the criteria for LB (Steere et al. 2003).
However, differences between the proportions of asymp-
tomatic infections in the United States and Europe may be
related to differences in study design, duration of follow-up,
diagnostic criteria, timing of postinfection treatment, anti-
body waning, and circulating genospecies. More data are
needed to understand the proportion of asymptomatic LB
infections, whether different genospecies vary in virulence,
and the impact of age, sex, and other factors on susceptibility
to clinical disease.
Our review has several limitations. Variations in study
design, populations sampled, time frame, sample size, and
diagnostic methods and strategies limit data interpretation and
comparability between studies. First, the articles we reviewed
encompassed countries of high and low endemicity and groups
at differing risk of exposure to ticks among the general pop-
ulation. For example, categorization of a sample as high risk
based on occupation may be inaccurate if the density of
infected ticks is not substantial in the region where the study
was conducted. Furthermore, seroprevalence data provide an
estimate of the prevalence of infection, but these results need
to be qualified based on testing accuracy and the duration of
antibodies. Seropositivity for antibodies to Bbsl reflects the
prevalence of prior or current Bbsl infection but is not neces-
sarily equivalent to clinical disease because not all infections
are symptomatic. Hence, seroprevalence may overestimate
the proportion of true clinical burden of the population that
has had symptomatic LB (Hammers-Berggren et al. 1994).
Immunoassays can yield false-positive results due to
detection of crossreacting antibodies to unrelated antigens
from bacterial, viral, parasitic, and some inflammatory con-
ditions (Branda and Steere 2021). The lack of a gold standard
test has significantly hampered the standardization of labo-
ratory tools to diagnose LB. Available assays may use whole-
cell or one or more recombinant antigens from a variety of
Bbsl species and show marked variability in sensitivity and
specificity (Kodym et al. 2018). Studies using single-tier
testing are thus prone to overestimation of LB seropreval-
ence (Branda and Steere 2021). Additionally, heterogeneity
between studies in terms of antibody testing strategies and
methods (including commercial vs. in-house) limits the
extent of meaningful comparisons.
Our review contributes to our understanding of the epi-
demiology of LB in Europe and highlights shortfalls and
impediments to understanding the disease burden. Standar-
dized LB testing strategies to monitor seroprevalence are
needed to facilitate geographic and temporal data compari-
sons. LB is a disease of place and needs to be monitored in
such a way that localized differences in tick exposure risk and
burden of disease can be detected and reported.
This study complements another systematic literature re-
view that evaluated the incidence of LB in European coun-
tries (Burn et al. 2023 in this issue) and provides information
for some countries, such as Turkey, for which incidence data
are not currently available. Although the ECDC started sur-
veillance on Lyme neuroborreliosis in 2018, studies mea-
suring the prevalence of antibodies to Bbsl infection in
European populations in some countries are currently the
only available source to monitor LB exposure and estimate
disease burden (European Center for Disease Prevention and
Control 2018). Seroprevalence, by providing a measure of the
prevalence of Bbsl infection, provides data that can be used to
estimate exposure to Bbsl among populations.
Our study provides an up-to-date picture of LB sero-
prevalence estimates in European countries. Seroprevalence
is also an important component of the body of information
that could guide intervention strategies, because monitoring
the disease burden at the local level is a necessity, particularly
in countries where LB is emerging.
216 BURN ET AL.
Data Availability
All results of this systematic literature review are derived
from the published literature as referenced.
Acknowledgments
The authors thank Margarita Riera-Montes (Chief Oper-
ations Officer and Medical Epidemiologist at P95) for her
support in developing the study protocol and in study
implementation. The authors thank Jo Wolter (Independent
Medical Writer, on behalf of P95 Pharmacovigilance &
Epidemiology) for her support in formatting this article.
Authors’ Contributions
L.B.: conceptualization, methodology, data curation, soft-
ware, formal analysis, investigation validation, resources,
writing original draft, writing review and editing, visualiza-
tion, supervision, and project administration. J.H.S.: con-
ceptualization, methodology, writing—review and editing,
project administration, supervision, and funding acquisition.
A.V.G.R.: data curation, formal analysis, and writing—
review and editing. T.M.P.T.: formal analysis, visualization.
A.P.: conceptualization, methodology, and writing—review
and editing. A.V.: conceptualization, methodology, and
writing—review and editing. M.A.F.: conceptualization,
methodology, and writing—review and editing. F.J.A.:
methodology, and writing—review and editing. B.D.G.:
writing—review and editing. J.C.M.: writing—review and
editing.
Author Disclosure Statement
J.H.S., F.J.A., B.D.G., A.P., A.V., M.A.F., and J.C.M. are
all employees of Pfizer and may hold stock options or stock
in Pfizer. All other authors declare no conflicts of interest.
Funding Information
This study was supported and jointly funded by Valneva
and Pfizer as part of their co-development of a Lyme Disease
vaccine.
Supplementary Material
Supplementary Table S1
Supplementary Table S2
Supplementary Table S3
Supplementary Table S4
Supplementary Table S5
References
Akar N, Cxalisxkan E, O
¨ztu
¨rk CE, Ankarali H, et al. Seropre-
valence of hantavirus and Borrelia burgdorferi in Du
¨zce
(Turkey) forest villages and the relationship with sociodemo-
graphic features. Turk J Med Sci 2019; 49:483–489.
Aslan Basxbulut E, Go
¨zalan A, So
¨nmez C, Cxo
¨plu
¨N, et al.
[Seroprevalence of Borrelia burgdorferi and tick-borne ence-
phalitis virus in a rural area of Samsun, Turkey]. Mikrobiyol
Bul 2012; 46:247–256.
Barreiro-Hurle L, Melon-Garcia S, Seco-Bernal C, Munoz-
Turrillas C, et al. Seroprevalence of Lyme disease in southwest
Asturias. Enferm Infecc Microbiol Clin 2020; 38:155–158.
Bazovska
´S, Guryc
ˇova
´D, Vy
´rostekova
´V, Jarekova
´J, et al.
[Antibodies against the causative agents of some natural focal
infections in blood donor sera from western Slovakia]. Epi-
demiol Mikrobiol Immunol 2010; 59:168–171.
Bazovska S, Machacova E, Spalekova M, Kontrosova S.
Reported incidence of Lyme disease in Slovakia and anti-
bodies to B. burgdorferi antigens detected in healthy popu-
lation. Bratisl Lek Listy 2005; 106:270–273.
Bennet L, Stjernberg L, Berglund J. Effect of gender on clinical
and epidemiologic features of Lyme borreliosis. Vector
Borne Zoonotic Dis 2007; 7:34–41.
Biletska H, Podavalenko L, Semenyshyn O, Lozynskyj I, et al.
Study of Lyme borreliosis in Ukraine. Int J Med Microbiol
2008; 298:154–160.
Bobe JR, Jutras BL, Horn EJ, Embers ME, et al. Recent
progress in Lyme disease and remaining challenges. Front
Med (Lausanne) 2021; 8:666554.
Bozkurt H, Cxiftc¸i HI, Gu
¨du
¨cu
¨g
ˇlu H, BerktasxM, et al.
Investigation of Borrelia burgdorferi seroprevalence in Van
region of Turkey. Turk J Immunol 2008; 13:5–9.
Branda JA, Steere AC. Laboratory diagnosis of Lyme borre-
liosis. Clin Microbiol Rev 2021; 34:e00018-19.
Branda JA, Strle F, Strle K, Sikand N, et al. Performance of
United States serologic assays in the diagnosis of Lyme
borreliosis acquired in Europe. Clin Infect Dis 2013; 57:333–
340.
Bucak O
¨, Koc¸og
˘lu ME, Tas
,
T, Mengelog
˘lu FZ. Evaluation of
Borrelia burgdorferi sensu lato seroprevalence in the prov-
ince of Bolu, Turkey. Turk J Med Sci 2016; 46:727–732.
Buczek A, Rudek A, Bartosik K, Szyman
´ska J, et al. Sero-
epidemiological study of Lyme borreliosis among forestry
workers in southern Poland. Ann Agric Environ Med 2009;
16:257–261.
Bura M, Bukowska A, Michalak M, Bura A, et al. Exposure to
hepatitis E virus, hepatitis A virus and Borrelia spp. infec-
tions in forest rangers from a single forest district in western
Poland. Adv Clin Exp Med 2018; 27:351–355.
Bus
ˇova
´A, Dorko E, Feketeova
´E, Rima
´rova
´K, et al. Asso-
ciation of seroprevalence and risk factors in Lyme disease.
Cent Eur J Public Health 2018; 26:S61–S66.
Carlsson H, Ekerfelt C, Henningsson AJ, Brudin L, et al.
Subclinical Lyme borreliosis is common in south-eastern
Sweden and may be distinguished from Lyme neuroborre-
liosis by sex, age and specific immune marker patterns. Ticks
Tick Borne Dis 2018; 9:742–748.
Centers for Disease Control and Prevention. Two-Tiered Test-
ing Decision Tree. 2011. Available at https://www.cdc.gov/
lyme/healthcare/clinician_twotier.html
Cetin E, Sotoudeh M, Auer H, Stanek G. Paradigm Burgenland:
risk of Borrelia burgdorferi sensu lato infection indicated
by variable seroprevalence rates in hunters. Wien Klin
Wochenschr 2006; 118:677–681.
Cikman A, Aydin M, Gulhan B, Karakecili F, et al. Geo-
graphical features and seroprevalence of Borrelia burgdorferi
in Erzincan, Turkey. J Arthropod Borne Dis 2019; 12:378–
386.
Cisak E, Chmielewska-Badora J, Zwolin
˜ski J, Wo
´jcik-Fatla A,
et al. Study on Lyme borreliosis focus in the Lublin region
(eastern Poland). Ann Agric Environ Med 2008; 15:327–
332.
Cora M, Kaklıkkaya N, Topbas
,
M, Cxan G, et al. Determination
of seroprevalence of Borrelia burgdorferi IgG in adult
population living in Trabzon. Balkan Med J 2017; 34:
47–52.
SEROPREVALENCE OF LYME BORRELIOSIS IN EUROPE 217
Cuellar J, Dub T, Sane J, Hytonen J. Seroprevalence of Lyme
borreliosis in Finland 50 years ago. Clin Microbiol Infect
2020; 26:632–636.
De Keukeleire M, Robert A, Kabamba B, Dion E, et al.
Individual and environmental factors associated with the
seroprevalence of Borrelia burgdorferi in Belgian farmers
and veterinarians. Infect Ecol Epidemiol 2016; 6:32793.
De Keukeleire M, Robert A, Luyasu V, Kabamba B, et al.
Seroprevalence of Borrelia burgdorferi in Belgian forestry
workers and associated risk factors. Parasit Vectors 2018; 11:
277.
DeepL SE. DeepL Translator, pro version. 2021. Available at
https://www.deepl.com/translator
Dehnert M, Fingerle V, Klier C, Talaska T, et al. Seropositivity
of Lyme borreliosis and associated risk factors: a population-
based study in children and adolescents in Germany
(KiGGS). PLoS One 2012; 7:e41321.
Di Renzi S, Martini A, Binazzi A, Marinaccio A, et al. Risk
of acquiring tick-borne infections in forestry workers from
Lazio, Italy. Eur J Clin Microbiol Infect Dis 2010; 29:1579–
1581.
Dong Y, Zhou G, Cao W, Xu X, et al. Global seroprevalence
and sociodemographic characteristics of Borrelia burgdorferi
sensu lato in human populations: a systematic review and
meta-analysis. BMJ Global Health 2022; 7:e007744.
Estrada-Pena A, Cutler S, Potkonjak A, Vassier-Tussaut M,
et al. An updated meta-analysis of the distribution and
prevalence of Borrelia burgdorferi s.l. in ticks in Europe. Int
J Health Geogr 2018; 17:41.
European Centre for Disease Prevention and Control. ECDC
comment: European Commission updates communicable
disease surveillance list—Lyme neuroborreliosis now under
EU/EEA surveillance. 2018. Available at https://www.ecdc
.europa.eu/en/news-events/ecdc-comment-european-commiss
ion-updates-communicable-disease-surveillance-list-lyme
Evidence Partners. DistillerSR version 2.35. 2021. Available at
https://www.evidencepartners.com
Gazi H, O
¨zku
¨tu
¨k N, Ecemis O
¨, Atasoylu G, et al. Sero-
prevalence of West Nile virus, Crimean-Congo hemorrhagic
fever virus, Francisella tularensis and Borrelia burgdorferi
in rural population of Manisa, western Turkey. J Vector
Borne Dis 2016; 53:112–117.
Glatz M, Golestani M, Kerl H, Mullegger RR. Clinical rele-
vance of different IgG and IgM serum antibody responses to
Borrelia burgdorferi after antibiotic therapy for erythema
migrans: long-term follow-up study of 113 patients. Arch
Dermatol 2006; 142:862–868.
Gu
¨nesxT, Poyraz O, Kaya S, Genc¸er L, et al. [Investigation
of vectors for Borrelia burgdorferi and Lyme seropositivity
in Sivas region]. Mikrobiyol Bul 2005; 39:503–508.
Hajek T, Libiger J, Janovska D, Hajek P, et al. Clinical and
demographic characteristics of psychiatric patients seroposi-
tive for Borrelia burgdorferi. Eur Psychiatry 2006; 21:118–
122.
Hammers-Berggren S, Lebech AM, Karlsson M, Svenungsson
B, et al. Serological follow-up after treatment of patients with
erythema migrans and neuroborreliosis. J Clin Microbiol
1994; 32:1519–1525.
Hjetland R, Nilsen RM, Grude N, Ulvestad E. Seroprevalence
of antibodies to Borrelia burgdorferi sensu lato in healthy
adults from western Norway: risk factors and methodological
aspects. APMIS 2014; 122:1114–1124.
Hofhuis A, Herremans T, Notermans DW, Sprong H, et al.
A prospective study among patients presenting at the general
practitioner with a tick bite or erythema migrans in the
Netherlands. PLoS One 2013; 8:e64361.
Huegli D, Moret J, Rais O, Moosmann Y, et al. Prospective
study on the incidence of infection by Borrelia burgdorferi
sensu lato after a tick bite in a highly endemic area of
Switzerland. Ticks Tick Borne Dis 2011; 2:129–136.
Johansson M, Manfredsson L, Wistedt A, Serrander L, et al.
Significant variations in the seroprevalence of C6 ELISA
antibodies in a highly endemic area for Lyme borreliosis:
evaluation of age, sex and seasonal differences. APMIS 2017;
125:476–481.
Jovanovic D, Atanasievska S, Protic-Djokic V, Rakic U, et al.
Seroprevalence of Borrelia burgdorferi in occupationally
exposed persons in the Belgrade area, Serbia. Braz J Micro-
biol 2015; 46:807–814.
Kalish RA, McHugh G, Granquist J, Shea B, et al. Persistence
of immunoglobulin M or immunoglobulin G antibody res-
ponses to Borrelia burgdorferi 10–20 years after active Lyme
disease. Clin Infect Dis 2001; 33:780–785.
Kaya AD, Parlak AH, Ozturk CE, Behcet M. Seroprevalence
of Borrelia burgdorferi infection among forestry workers and
farmers in Duzce, north-western Turkey. New Microbiol
2008; 31:203–209.
Kiewra D, Szymanowski M, Zalewska G, Dobracka B, et al.
Seroprevalence of Borrelia burgdorferi in forest workers
from inspectorates with different forest types in Lower Sile-
sia, SW Poland: preliminary study. Int J Environ Health Res
2018; 28:502–510.
Kocbach PP, Kocbach BP. [Prevalence of Lyme disease among
forestry workers]. Med Pr 2014; 65:335–341.
Kodym P, Kurzova Z, Berenova D, Picha D, et al. Serological
diagnostics of Lyme norreliosis: comparison of universal
and borrelia species-specific tests based on whole-cell and
recombinant antigens. J Clin Microbiol 2018; 56:e00601-18.
Kr
ˇı
´z
ˇB, Maly
´M, Bala
´tova
´P, Kodym P, et al. A serological study
of antibodies to Anaplasma phagocytophilum and Borrelia
burgdorferi sensu lato in the sera of healthy individuals col-
lected two decades apart. Acta Parasitol 2018; 63:33–39.
Krstic
´M, Stajkovic
´N. [Risk for infection by Lyme disease
cause in green surfaces maintenance workers in Belgrade].
Vojnosanit Pregl 2007; 64:313–318.
Kuchynka P, Palecek T, Grus T, Lindner J, et al. Absence of
Borrelia burgdorferi in the myocardium of subjects with
normal left ventricular systolic function: a study using PCR
and electron microscopy. Biomed Pap Med Fac Univ Palacky
Olomouc Czech Repub 2016; 160:136–139.
Lakos A, Igari Z, Solymosi N. Recent lesson from a clinical and
seroepidemiological survey: low positive predictive value of
Borrelia burgdorferi antibody testing in a high risk popula-
tion. Adv Med Sci 2012; 57:356–363.
Laud P. Confidence intervals for comparisons of binomial or
Poisson rates. 2021. Available at https://cran.r-project.org/
web/packages/ratesci/ratesci.pdf
Lernout T, Kabamba-Mukadi B, Saegeman V, Tre
´-Hardy M,
et al. The value of seroprevalence data as surveillance tool for
Lyme borreliosis in the general population: the experience of
Belgium. BMC Public Health 2019; 19:597.
Lledo L, Gimenez-Pardo C, Gegundez MI. Screening of for-
estry workers in Guadalajara province (Spain) for antibodies
to lymphocytic choriomeningitis virus, hantavirus, Rickettsia
spp. and Borrelia burgdorferi. Int J Environ Res Public
Health 2019; 16:4500.
Machcin
´ska M, Noworyta J, Brasse-Rumin M, Gago J, et al.
Prevalence of Yersinia spp., Chlamydia trachomatis,
218 BURN ET AL.
Chlamydophila pneumoniae and Borrelia burgdorferi anti-
bodies in healthy blood donors’ sera. Reumatologia 2013; 51:
422–428.
Magnaval JF, Leparc-Goffart I, Gibert M, Gurieva A, et al.
A serological survey about zoonoses in the Verkhoyansk area,
northeastern Siberia (Sakha Republic, Russian Federation).
Vector Borne Zoonotic Dis 2016; 16:103–109.
Magnavita N, Capitanelli I, Ilesanmi O, Chirico F. Occupational
Lyme disease: a systematic review and meta-analysis.
Diagnostics (Basel) 2022; 12:296.
Margos G, Fingerle V, Reynolds S. Borrelia bavariensis:
Vector switch, niche invasion, and geographical spread of a
tick-borne bacterial parasite. Front Ecol Evol 2019; 7:401.
Margos G, Vollmer SA, Cornet M, Garnier M, et al. A new
Borrelia species defined by multilocus sequence analysis of
housekeeping genes. Appl Environ Microbiol 2009; 75:5410–
5416.
Markowicz M, Reiter M, Gamper J, Stanek G, et al. Persistent
anti-Borrelia IgM antibodies without Lyme borreliosis in the
clinical and immunological context. Microbiol Spectr 2021;
9:e0102021.
Marques AR. Revisiting the Lyme disease serodiagnostic
algorithm: the momentum gathers. J Clin Microbiol 2018; 56:
e00749-18.
Marques AR, Strle F, Wormser GP. Comparison of Lyme dis-
ease in the United States and Europe. Emerg Infect Dis 2021;
27:2017–2024.
Motiejunas L, Bunikis J, Barbour AG, Sadziene A. Lyme bor-
reliosis in Lithuania. Scand J Infect Dis 1994; 26:149–155.
Munro H, Mavin S, Duffy K, Evans R, et al. Seroprevalence
of Lyme borreliosis in Scottish blood donors. Transfus Med
2015; 25:284–286.
Oteiza-Olaso J, Tiberio-Lopez G, Martinez de Artola V,
Belzunegui-Otano T. [Seroprevalence of Lyme disease in
Navarra, Spain]. Med Clin (Barc) 2011; 136:336–339.
Pan
´czuk A, Tokarska-Rodak M, Plewik D, Paszkiewicz J. Tick
exposure and prevalence of Borrelia burgdorferi antibodies
among hunters and other individuals exposed to vector ticks
in eastern Poland. Rocz Panstw Zakl Hig 2019; 70:161–
168.
Parlak M, Bayram Y, Cxıkman A, Ceylan N, et al. [Seroposi-
tivity of Borrelia burgdorferi in risky groups in Van region,
Turkey]. Mikrobiyol Bul 2015; 49:439–445.
Parm U
¨, Niitva
¨gi E, Beljaev K, Aro T, et al. Lyme borreliosis in
Saaremaa. Eesti Arst 2015; 94:203–210.
Pawelczyk A, Bednarska M, Kowalska JD, Uszynska-Kaluza B,
et al. Seroprevalence of six pathogens transmitted by the
Ixodes ricinus ticks in asymptomatic individuals with HIV
infection and in blood donors. Sci Rep 2019; 9:2117.
Peltomaa M, McHugh G, Steere AC. Persistence of the antibody
response to the VlsE sixth invariant region (IR6) peptide of
Borrelia burgdorferi after successful antibiotic treatment of
Lyme disease. J Infect Dis 2003; 187:1178–1186.
Perry KC. DigitalCommons@UMaine. Acting out of Lyme:
characterizing the human dimensions of Lyme disease inter-
ventions. 2021. Available at https://digitalcommons.library
.umaine.edu/etd/3485
Piacentino JD, Schwartz BS. Occupational risk of Lyme dis-
ease: an epidemiological review. Occup Environ Med 2002;
59:75–84.
Podsiadly E, Chmielewski T, Karbowiak G, Kedra E, et al. The
occurrence of spotted fever rickettsioses and other tick-borne
infections in forest workers in Poland. Vector Borne Zoonotic
Dis 2011; 11:985–989.
PRISMA. Transparent Reporting of Systematic Reviews and
Meta-Analyses. 2020. Available at https://www.prisma-
statement.org
Rauter C, Hartung T. Prevalence of Borrelia burgdorferi sensu
lato genospecies in Ixodes ricinus ticks in Europe: a metaa-
nalysis. Appl Environ Microbiol 2005; 71:7203–7216.
Richter D, Matuschka FR. Perpetuation of the Lyme disease
spirochete Borrelia lusitaniae by lizards. Appl Environ
Microbiol 2006; 72:4627–4632.
Rojko T, Ruzic-Sabljic E, Strle F, Lotric-Furlan S. Prevalence
and incidence of Lyme borreliosis among Slovene forestry
workers during the period of tick activity. Wien Klin
Wochenschr 2005; 117:219–225.
Ruiz VH, Edjolo A, Roubaud-Baudron C, Jaulhac B, et al.
Association of seropositivity to Borrelia burgdorferi with the
risk of neuropsychiatric disorders and functional decline in
older adults: the aging multidisciplinary investigation study.
JAMA Neurol 2020; 77:210–214.
Sonnleitner ST, Margos G, Wex F, Simeoni J, et al. Human
seroprevalence against Borrelia burgdorferi sensu lato in two
comparable regions of the eastern Alps is not correlated to
vector infection rates. Ticks Tick Borne Dis 2015; 6:221–227.
Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, et al. Lyme
borreliosis: clinical case definitions for diagnosis and man-
agement in Europe. Clin Microbiol Infect 2011; 17:69–79.
Steere AC, Sikand VK, Schoen RT, Nowakowski J. Asympto-
matic infection with Borrelia burgdorferi. Clin Infect Dis
2003; 37:528–532.
Steere AC, Strle F, Wormser GP, Hu LT, et al. Lyme borre-
liosis. Nat Rev Dis Primers 2016; 2:16090.
Strnad M, Honig V, Ruzek D, Grubhoffer L, et al. Europe-wide
meta-analysis of Borrelia burgdorferi sensu lato prevalence
in questing Ixodes ricinus ticks. Appl Environ Microbiol
2017; 83:e00609-17.
Thorin C, Rigaud E, Capek I, Andre
´-Fontaine G, et al. [Sero-
prevalence of Lyme borreliosis and tick-borne encephalitis in
workers at risk, in eastern France]. Med Mal Infect 2008; 38:
533–542.
Thortveit EA-O, Aase A, Petersen LB, Lorentzen A
˚RA-O,
et al. Subjective health complaints and exposure to tick-borne
infections in southern Norway. Acta Neurol Scand 2020; 142:
260–266.
Tokarska-Rodak M, Plewik D, Kozioł-Montewka M, Szepeluk
A, et al. [Risk of occupational infections caused by Borrelia
burgdorferi among forestry workers and farmers]. Medycyna
Pracy 2014; 65:109–118.
Tomao P, Ciceroni L, D’Ovidio MC, De Rosa M, et al. Pre-
valence and incidence of antibodies to Borrelia burgdorferi
and to tick-borne encephalitis virus in agricultural and
forestry workers from Tuscany, Italy. Eur J Clin Microbiol
Infect Dis 2005; 24:457–463.
Uyanık MH, Yazgı H, Ayyıldız A. Seropositivity of Lyme
disease in Erzurum province, Turkey. Turk J Infect 2009; 23:
69–72.
van Beek J, Sajanti E, Helve O, Ollgren J, et al. Population-
based Borrelia burgdorferi sensu lato seroprevalence and
associated risk factors in Finland. Ticks Tick Borne Dis 2018;
9:275–280.
Van den Wijngaard CC, Hofhuis A, Simo
˜es M, Rood E, et al.
Surveillance perspective on Lyme borreliosis across the
European Union and European economic area. Eurosur-
veillance 2017; 22:30569.
van Gorkom T, Kremer K, Voet W, Notermans DW, et al.
Disagreement between the results from three commercial
SEROPREVALENCE OF LYME BORRELIOSIS IN EUROPE 219
tests for the detection of Borrelia-specific serum antibodies in
the Netherlands associated with antibiotic treatment for Lyme
borreliosis: a retrospective study. Eur J Clin Microbiol Infect
Dis 2017; 36:2137–2146.
Vestrheim DF, White RA, Aaberge IS, Aase A. Geographical
differences in seroprevalence of Borrelia burgdorferi anti-
bodies in Norway, 2011–2013. Ticks Tick Borne Dis 2016; 7:
698–702.
Wilhelmsson P, Fryland L, Lindblom P, Sjowall J, et al.
A prospective study on the incidence of Borrelia burgdorferi
sensu lato infection after a tick bite in Sweden and on the
Aland Islands, Finland (2008–2009). Ticks Tick Borne Dis
2016; 7:71–79.
Wilking H, Fingerle V, Klier C, Thamm M, et al. Antibodies
against Borrelia burgdorferi sensu lato among adults, Ger-
many, 2008–2011. Emerg Infect Dis 2015; 21:107–110.
Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and
serological diagnosis of Lyme borreliosis. FEMS Immunol
Med Microbiol 2007; 49:13–21.
World Health Organization. Annex: regional classifications.
2022. Available at https://cdn.who.int/media/docs/default-
source/air-pollution-documents/air-quality-and-health/country-
groupings-database-2022.pdf
Zaja˛c V, Pinkas J, Wo
´jcik-Fatla A, Dutkiewicz J, et al. Pre-
valence of serological response to Borrelia burgdorferi in
farmers from eastern and central Poland. Eur J Clin Microbiol
Infect Dis 2017; 36:437–446.
Za
´kutna
´L, Dorko E, Mattova
´E, Rima
´rova
´K. Sero-
epidemiological study of Lyme disease among high-risk
population groups in eastern Slovakia. Ann Agric Environ
Med 2015a; 22:632–636.
Za
´kutna
´L, Dorko E, Rima
´rova
´K, Kizekova
´M. Pilot cross-
sectional study of three zoonoses (Lyme disease, tularaemia,
leptospirosis) among healthy blood donors in eastern Slova-
kia. Cent Eur J Public Health 2015b; 23:100–106.
Address correspondence to:
James H. Stark
Pfizer Vaccines Medical Development,
Scientific and Clinical Affairs
500 Arcola Road
Collegeville, PA 19460
USA
E-mail: james.h.stark@pfizer.com
220 BURN ET AL.
